1. Field of the Invention
The present invention relates in general to a method and apparatus for obtaining an optical tomographic image of a sentinel lymph node, and in particular, to detecting the sentinel lymph node, into which tumor cells first enter the lymph system from the primary nidus of a tumor, and obtaining an optical tomographic image of the sentinel lymph node.
2. Description of the Related Art
Recent years have seen increased rates in the early detection of cancer and the like, and cancerous and other diseased tissues are frequently surgically removed in the early stages of a disease. Generally, the objective of early surgical removal of cancerous tissue is the complete arresting of the disease, and frequently, in addition to the diseased tissue, a plurality of lymph nodes in the area surrounding the diseased tissue, from which there is a suspected danger of metastasis of the disease, are also removed. In addition, a test for pathology is performed on the excised lymph nodes to confirm whether or not the disease has metastasized thereto, and the course of post-surgical treatment is determined.
Due to the fact that it is not known whether or not the disease has metastasized to the lymph nodes during the performance of the surgical removal thereof, a plurality of lymph nodes in the surrounding vicinity of the diseased tissue is removed, and the burden on the patient is therefore great. Further, in the early stages of breast cancer, for example, the rate of metastasis of the disease to lymph nodes is 20 percent; for the 80 percent of the patients in whom the disease has not metastasized to the lymph nodes, the removal thereof is unnecessary.
In recent years, both the complete halting of the disease through surgical removal of the cancerous tissue and the preservation of the QOL (Quality of Life) of the patient are sought. To this end, one surgical method that has received much attention, which is aimed at preventing unnecessary removal of lymph nodes, is sentinel node navigation surgery. Hereinafter, a simple explanation of sentinel node navigation surgery will be given.
For cases in which cancer has metastasized to lymph nodes, it has become clear, in light of recent research, that it does not metastasize randomly, but is metastasize through the lymph system to the lymph nodes according to a set pattern. The first lymph node into which cancer cells enter from the primary nidus of a cancer is called a sentinel lymph node; it is held that for cases in which cancer has metastasized to the lymph nodes, the cancer has definitely metastasized to a sentinel lymph node.
Accordingly, by finding and excising the sentinel lymph node in a cancer removal surgery performed in the early stages of the disease, and preparing a sample of the excised sentinel lymph node and expediently performing a test for pathology thereon, it can be determined whether or not the cancer has metastasized to the lymph nodes.
For cases in which the cancer is determined not to have metastasized to the lymph nodes, it is unnecessary to remove the remaining lymph nodes. For cases in which the cancer is found to have metastasized to the lymph nodes, depending upon the conditions, a plurality of lymph nodes are surgically removed from the vicinity surrounding the diseased tissue.
By performing sentinel node navigation surgery, it becomes unnecessary to remove lymph nodes of patients for whom it has been determined that cancer has not metastasized to the sentinel lymph node, and the burden on such patients is thereby reduced. Moreover, this type of surgery is not limited to breast cancer, but can be employed in conjunction with open gastrointestinal tract surgery or surgical procedures utilizing a laparoscope.
One conventional method of detecting the lymph node is the colorant method, employing a blue colorant. According to this method, a blue colorant is locally injected, endermically or by use of an endoscope, into the vicinity surrounding the diseased area directly preceding the performance of cancer removal surgery; the sentinel lymph node dyed by the blue colorant is visually detected. Another known method is the RI method, wherein a radioisotope is employed as a tracer.
According to the RI method, a radioisotope is locally injected, endermically or by use of an endoscope, on the day prior to surgery into the vicinity surrounding the diseased area. The injected radioisotope advances from the position at which it was injected towards the lymph nodes and stays for a set duration at the sentinel lymph node. A few hours after the radioisotope is injected a lymphosynthography is performed, and the approximate position is marked. When the surgery to remove the cancer is performed, the marked position is cut open, and employing a gamma-probe, the gamma radiation emitted by the lymph nodes in the vicinity of the opened position is detected; the lymph node emitting the most gamma radiation is detected as the sentinel lymph node.
Further, in recent years fluorescent colorant methods employing fluorescent colorants have been proposed for detecting diseased tissue: For example, an embodiment of a sentinel lymph node detection apparatus has been disclosed in Japanese Patent Application No. 2000-124600, by the inventors of the present invention, wherein a cyanine colorant is administered to a living tissue, and by irradiation thereof by an excitation light, the diseased tissue is detected.
However, according to aforementioned conventional sentinel lymph node navigational surgery, when a determination is to be made as to whether or not cancer has metastasized to the sentinel lymph node, an on-the-spot diagnosis of the cause of the disease is performed by surgically removing the sentinel lymph node, preparing a sample thereof and examining an image of the cells contained in said sample. However, as per the case in which the early detection of breast cancer is performed as described above, for example, because the rate of metastasis of the disease to lymph nodes is 20 percent, for the 80 percent of the patients in whom the disease has not metastasized to the lymph nodes, the removal of the sentinel lymph node is unnecessary. Although there is a strong demand, accompanying the trend in recent years to preserve the QOL of the patient, for a sentinel lymph node detection method in which it is not necessary to surgically remove the sentinel lymph node, the conventional sentinel lymph node detection method and apparatus described above only disclose methods of lymph node detection, and there is no mention therein of a method or apparatus in wherein the test for pathology is performed in a manner in which the sentinel lymph node is not surgically removed.
The present invention has been developed in consideration of the circumstances described above, and it is a primary objective of the present invention to provide a sentinel lymph node optical tomographic image obtaining method and apparatus for obtaining an image of the cells of the sentinel lymph node for use in performing a test for pathology.
The method of obtaining an optical tomographic image of a sentinel lymph node according to the present invention comprises the steps of detecting the sentinel lymph node residing in the vicinity of a diseased tissue (hereinafter referred to as a target subject), scanning the detected sentinel lymph node with a signal-light having a coherence length of 5 um or less, and obtaining an ultra high resolution optical tomographic image of the sentinel lymph node by using the reflected-light reflected from a predetermined depth of said sentinel lymph node and the interference caused by the signal-light and a reference-light of a frequency slightly different from that of the signal-light.
Further, the method of detecting the sentinel lymph node can be based on a fluorescent-light image obtained of the fluorescent light, which is close to the near-infrared wavelength band, emitted from near-infrared fluorescent colorant that has been injected into an examination area of the target subject in the vicinity of the diseased portion, which includes the sentinel lymph node, upon the irradiation thereof by an excitation light having a wavelength within the wavelength range causing excitation of the near-infrared fluorescent colorant, however, it is not limited thereto; a colorant method employing a blue colorant, etc., or an RI method employing a radio isotope as a tracer can also be employed.
Here, the referents of the expression xe2x80x9cbased on a fluorescent-light image obtained of the fluorescent light, which is close to the near-infrared wavelength bandxe2x80x9d include a method, for example, wherein the intensity of the fluorescent light of each pixel constituting a fluorescent-light image formed of fluorescent light of a wavelength near the near-infrared wavelength range is compared to every other pixel constituting said fluorescent-light image, and the pixel detected as having the highest intensity is recognized as representing the sentinel lymph node, a method wherein a fluorescent-light image is converted to a visible image representing the intensity of the fluorescent light as a gradient, and detecting the sentinel lymph node by visually examining said image, etc.
Further, the scanning-position to be scanned by the signal-light can be matched the position of the sentinel lymph node detected based on the fluorescent-light image. Here, the referents of the expression xe2x80x9cthe scanning-position to be scanned by the signal-light can be matched the position of the sentinel lymph node detected based on the fluorescent-light imagexe2x80x9d include any method wherein the scanning-position to be scanned by the signal-light is determined without having to perform a manual operation therefor, and is automatically matched to the position of the sentinel lymph node detected based on the fluorescent-light image: For example, a method comprising the steps of converting a fluorescent-light image is to a visible image and then displaying said visible image on a monitor, confirming the position of the sentinel lymph node by viewing the image displayed on the monitor, inputting the position of the pixel corresponding to the position of the sentinel lymph node, and setting as the scanning-position to be scanned by the signal-light the position of the target subject that matches the position of the pixel detected as representing the sentinel lymph node, a method comprising the steps of obtaining the pixel having the highest intensity value by performing an image processing operation, and setting as the scanning-position to be scanned by the signal-light the position of the target subject that matches the position of the pixel detected as representing the sentinel lymph node, etc.
The sentinel lymph node optical tomographic image obtaining apparatus according to the present invention comprises: a sentinel lymph node detecting means; and an OCT means for scanning the detected sentinel lymph node with a signal-light, which is a low-coherence light having a coherence length of 5 um or less, and obtaining an ultra high resolution optical tomographic image of the sentinel lymph node, using the reflected-light reflected from a predetermined depth of the sentinel upon the irradiation thereof by the signal-light, and the interference caused between the signal-light and a reference-light which has a slight difference in frequency from that of the signal-light. OCT stands for Optical Coherence Tomography, which is defined as the obtaining of an optical tomographic image by using the interference caused by a low-coherence light. For a detailed explanation of OCT, refer to an article in xe2x80x9cO Plus Exe2x80x9d Vol.21, No. 7, pp. 802-04, by Masamitsu Haruna.
Further, an OCT means employing an optical fiber light source for emitting low-coherence light has been disclosed in Japanese Patent Application 2000-67264 filed by the inventors of the present invention. According to said OCT apparatus: the low-coherence light emitted from aforementioned light source is separated into a signal-light and a reference-light; the wavelength of the signal-light or the reference-light is slightly shifted by use of a Piezo element or the like; the target subject is irradiated with the signal-light and interference is caused between the reflected-light reflected from said target subject at a predetermined depth and the reference-light; the signal strength of the light-beat produced due to said interference is measured by a heterodyne wave detection; and the tomographic data based on the reflectance ratio of the signal-light is obtained; wherein, by very slightly moving a movable mirror, etc., disposed above the optical path of the reference-light, causing the length of the optical path of the reference-light to change slightly, and the data for a target subject can be obtained for a depth at where the length of the optical path of the reference-light and the length of the optical path of the signal-light can be made to be equal. Further, by shifting in intervals of a microscopic distance the position of the target subject to be irradiated by the signal-light, and taking a measurement at each position shifted to, that is, by scanning the target subject with the signal-light, an optical tomographic image of the scanned position can be obtained.
The sentinel lymph node detecting means comprises: an excitation light emitting means for projecting an excitation light, which has a wavelength within the wavelength range causing excitation of a near-infrared fluorescent colorant that emits fluorescent light having a wavelength band near the near-infrared wavelength band, onto the target subject including the sentinel lymph node and into the vicinity of which the near-infrared fluorescent colorant has been injected in advance, an image obtaining means for obtaining an image formed of the near-infrared fluorescent light having emitted from the target subject, and a sentinel lymph node detecting means for detecting the sentinel lymph node based on the fluorescent-light image obtained by the image obtaining means.
Here, the referent of the expression xe2x80x9ca sentinel lymph node detecting means for detecting the sentinel lymph node based on thefluorescent-lightimageobtainedbytheimageobtainingmeansxe2x80x9d can be, for example, a means for comparing, by use of image processing, the intensity of each pixel of a fluorescent-light image obtained by the image obtaining means and recognizing the pixel detected as having the highest intensity as the pixel representing the sentinel lymph node.
Further, the OCT means can be provided with a scanning-position control means for matching the scanning-position to be scanned by the signal-light to the position of the sentinel lymph node detected, based on the fluorescent-light image, by the sentinel lymph node detecting means.
Here, the referent of the expression xe2x80x9ca scanning-position control means for matching the scanning-position to be scanned by the signal-light to the position of the sentinel lymph node detected, based on the fluorescent-light image, by the sentinel lymph node detecting meansxe2x80x9d can be any means which automatically, that is, requiring no manual operation to determine the scanning-position to be scanned by the signal-light, matches the position to be scanned by the signal-light to the position of the sentinel lymph node detected based on the fluorescent-light image: for example, a means for matching the scanning-position to be scanned by the signal-light to the position of the target subject corresponding to the position of the pixel within a fluorescent-light image detected as having the highest intensity, which is the pixel representing the sentinel lymph node.
It is preferable that the low-coherence light is of a wavelength within the wavelength range of 600-1700 nm.
Note that according to the present invention, the light source for emitting the low-coherence light is not limited to any specific light source; any light source that emits a low-coherence light having a coherence length of 5 um or less can be employed.
According to the method and apparatus for obtaining a sentinel lymph node optical tomographic image according to the present invention: a detected sentinel lymph node is scanned with a signal-light, which is a low-coherence light having a coherence length of 5 um or less; and an ultra high-resolution optical tomographic image of the sentinel lymph node is obtained. Because an ultra high-resolution optical tomographic image of the sentinel lymph node can be obtained by scanning the sentinel lymph node with the signal-light, it is not necessary to surgically remove the sentinel lymph node. Further, although the resolution of the ultra high-resolution optical tomographic image of the sentinel lymph node is dependent upon the coherence length of the low-coherence light, by using a low-coherence light having a coherence length of 5 um or less, the resolution of the ultra high-resolution optical tomographic image can be improved to the cellular level. Accordingly, by application of the method and apparatus for obtaining a sentinel lymph node optical tomographic image according to the present invention, an ultra high-resolution optical tomographic image of the sentinel lymph node, which attains resolution to the cellular level, can be obtained without the surgical removal thereof. If a test for pathology is carried out, by a pathologist or a pathology diagnostic apparatus, employing the ultra high-resolution optical tomographic image of the sentinel lymph node, for cases in which it is determined that the disease has not metastasized to the sentinel lymph node, that is, for cases in which it is not necessary to surgically remove the sentinel lymph node, the surgery can be completed without surgically removing the sentinel lymph node.
Further, for cases in which the detecting of the sentinel lymph node is carried out based on a near-infrared fluorescent-light image obtained of the fluorescent light having a wavelength near the near-infrared wavelength band emitted from a target subject, into the vicinity of which a near-infrared fluorescent colorant has been injected in advance into a target subject that includes the sentinel lymph node, upon the irradiation thereof by an excitation light having a wavelength near the wavelength range of light that causes excitation of a near-infrared fluorescent colorant, the target area including the sentinel lymph node can be rendered as an image, and the detection of the sentinel lymph node can be performed easily and efficiently.
Still further, when the sentinel lymph node is detected based on the aforementioned fluorescent-light image, because the position of the sentinel lymph node can be specified as the position of the pixel representative thereof occurring in the fluorescent-light image, the position within the target subject that corresponds to the position of said pixel can be automatically matched to the scanning-position to be scanned by the signal-light; whereby the necessity to perform a troublesome manual operation therefor is eliminated, an ultra high-resolution optical tomographic image can be obtained expediently and the overall benefit to patient and operator obtained by application of the present invention is improved.
Additionally, if the low-coherence light has a wavelength in the 600-1700 nm wavelength range, the signal-light exhibits desirable transmittance and dispersion characteristics with respect to the body of a patient, a desired optical tomographic image data can be obtained.